Skin ages together with chronological aging like other living tissues, and its aging is accelerated by exposure to ultraviolet radiation. Recent research revealed that chronological aging-induced skin aging and ultraviolet radiation-induced skin aging shared several important molecular biological aspects.
The skin includes, from the outer side, the corneal layer, the epidermal layer, the dermis layer, and the subcutaneous tissue. The epidermal layer is constantly replaced with new epidermal cells which are born in the deepest epidermal basal layer and migrate up in an outward direction (this is called a turnover of epidermal cells). Known as factors of skin aging are a decrease in turnover of epidermal cells constituting the epidermal layer, and a decrease in collagen that exist between fibroblast cells in the dermis layer (Arch Dermatol. 2002; 138: 1462-1470). Collagen is a main component of the dermis layer, and is involved in maintaining of skin elasticity. It has been known that the amount of collagen in skin is decreased by chronological aging and damage due to ultraviolet radiation; consequently, the skin elasticity is lowered, and wrinkle formation and skin aging are accelerated. It is also known that drying causes thickening of the corneal layer and the epidermal layer and the delay in peeling off of the corneal layer causes shallow wrinkle formation (J. Dermatol. Sci. 2001; 27 Suppl 1: S19-25). Spot and sagging of skin are also main symptoms of skin aging and wrinkle formation is a major element of the skin aging. Accordingly, various methods have been conventionally taken for the prevention of such wrinkling, which includes, for example, a method of promoting synthesis of collagen fibers that support the skin structure and preventing a decrease in the collagen fibers. Moreover, promoting regeneration of the corneal layer and epidermal cells which is involved in maintaining moisture and barrier function of skin, i.e., promoting replacement of the epidermal layer and the corneal layer (epidermal turnover) (epidermal cell activation), is also thought as an effective wrinkle prevention method.
At present, generally widespread means for preventing wrinkles include components that provide moisture to skin, and cosmetics for external application in which a component for maintaining the elasticity is blended. Such cosmetics contain, for example, mucopolysaccharides such as hyaluronic acid or chondroitin sulfate, collagen, vitamins, amino acids, ceramides, or the like.
Recently, also developed are health and beauty foods which are considered to be good for skin. The examples includes: a collagen production promoting agent including an enzyme-hydrolyzed product of lactoferrin or an enzyme-hydrolyzed product of lactoperoxidase (JP-A 2004-331564, JP-A 2004-331565); a health and beauty food (JP-A 2006-143671) characterized by including mucopolysaccharides; and the like.
As low-molecular-weight compounds for promoting production of collagen, vitamins A such as retinoic acid and its derivative retinol are known (Arch Dermatol. 2007 May; 143(5): 606-12). Furthermore, there is a collagen-production promoting technique utilizing a peptide or an amino acid as a highly safe low-molecular-weight compound. For example, developed are a collagen-production promoting composition containing as an active ingredient peptides which is a collagen hydrolysate with collagenase (JP-A 2007-91637), and Leu-Glu-His-Ala derived from a soy protein or the like (JP-A 2007-145795). Moreover, also known is a beauty food in which three amino acids, L-proline, L-alanine and L-glycine, are blended at a ratio close to that in human skin collagen (JP-A 2001-224334).
Still furthermore, WO2006/000350 describes a milk protein hydrolysate containing a peptide of which terminal is proline, which has a cosmetic effect. This document describes that a cosmetic including a high content of peptides having prolines at the carboxyl terminals is effective. However, active ingredients are not specified, and absorption in the intestinal tract at the time of oral ingestion is not mentioned at all.
On the other hand, it has been presented that beauty effects such as suppressed ultraviolet-radiation sensitivity of skin, epidermal cell-differentiation promotion, and moisturization are observed in fermentation metabolites, such as fermented milk and whey, produced by a lactic acid bacterium (WO2006/095764, WO2006/137513, JP-A 2005-206578).
Furthermore, as a method for examining the absorption of drugs, peptides and the like, in the intestinal tract, an in vitro test system is known which uses permeability through a cell layer of Caco-2 cells which are epithelial cells derived from human colon cancer. The drug permeability test system using a monolayer cell culture of Caco-2 cells is known to be useful in predicting and evaluating in vivo drug absorption (Pharm Res. 1997 April; 14(4): 486-91).